Luminal Flow in the Connecting Tubule induces Afferent Arteriole Vasodilation

Abstract

BackgroundRenal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF--whether NaCl concentration, independent luminal flow, or the combined total sodium delivery--is still unclear. We hypothesized that increasing luminal flow in the CNT induces CNTGF via O2- generation and ENaC activation. MethodsRabbit afferent arterioles (Af-Arts) with adjacent CNTs were microperfused ex-vivo with variable flow rates and sodium concentrations ranging from 0.05). Multiple linear regression modeling (R2=0.51;p<0.001) demonstrated that tubular flow ({beta}=0.163 {+/-} 0.04;p<0.001) and sodium concentration ({beta}=0.14 {+/-} 0.03;p<0.001) are independent variables that induce afferent arteriole vasodilation. Tempol reduced flow-induced CNTGF, and L-NAME did not influence this effect. ConclusionIncreased luminal flow in the CNT induces CNTGF activation via ENaC, partially due to flow-stimulated O2-production and independent of nitric oxide synthase (NOS) activity.